Recombinant techniques have allowed the discovery of artificial and natural proteins that have broad applications in the development of therapeutics, diagnostic agents (e.g., for imaging or binding assays), enzymes, and agents for affinity separations. One such recombinant technique is the construction of nucleic acid libraries that include diverse sequence content. Libraries can be screened by hybridization, genetic complementation, and polypeptide expression, among other activities. One challenge for the development of recombinant proteins is the rapid identification of proteins that are functional in the context of their ultimate therapeutic or industrial use.
One exemplary class of proteins being developed as therapeutics includes antibodies. The properties of antibodies are being exploited in order to design agents that bind to human target molecules, so-called, “self-antigens.” For example, a number of monospecific antibodies have been approved as human therapeutics. These include Orthoclone OKT3, which targets CD3 antigen; ReoPro, which targets GP IIb/IIIa; Rituxan, which targets CD20; Zenapax and Simulect, which target interleukin-2 receptors; Herceptin, which targets the HER2-receptor; Remicade, which targets tumor necrosis factor; Synagis, which targets the F protein of respiratory syncytial virus; Mylotarg, which targets CD33; and Campath, which targets CD52 (see, e.g., Carter (2001) Nature Reviews 1:118-129; Ezzell (2001) Scientific American October 2001, pages 36-41; Garber (2001) Nat. Biotechnol. 19:184-185).